P1329: POST-TRANSPLANT CYCLOPHOSPHAMIDE (PT-CY) VERSUS ANTITHYMOCYTE GLOBULIN (ATG) AS GVHD PROPHYLAXIS FOR MATCHED UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION.
Authors: F. Dachy, S. Furst, B. Calmels, T. Pagliardini, S. Harbi, B. Bouchacourt, A. Calleja, C. Lemarie, A. Collignon, G. Morel, F. Legrand, E. Bekrieva, A. Granata, P. J. Weiller, C. Chabannon, J. M. Schiano de Collela, N. Vey, D. Blaise, R. Devillier
Journal: HemaSphere (2022)

Background: In recent years, post-transplant cyclophosphamide (PT-Cy) has become an essential component for GVHD prophylaxis in T-cell replete haploidentical (HRD) stem cell transplantation. It is now being evaluated in unrelated donor (UD) transplants. Aims: Our objective is to evaluate the efficacy of PT-Cy as part of GVHD prophylaxis in the setting of 10/10 UD allo-HSCT. Methods: We reported the outcomes of a HLA-10/10 matched unrelated donor (MUD) allo-HSCT cohort, treated with PT-Cy (n=30) between April 2020 and July 2021, and performed a retrospective comparison with an historical control group treated with ATG (n=64). Results: Among the whole 94 patients, the median age was 57.5 (18-75), 43 (45%) patients had acute myeloid leukemia, 12 (13%) had myelodysplastic syndrome, 12 (13 %) had acute lymphoid leukemia, 27 (29%) had lymphoma. Median HCT-CI score was 3. All patients received peripheral blood stem cells as graft source. There was no significant difference in these baseline characteristics between both groups. In the PT-Cy group, 21 (70%) and 9 (30%) patients received non-myeloablative (fludarabine cyclophosphamide 2 Gray TBI) and thiotepa busulfan fludarabine based conditioning regimens, respectively. They were given cyclosporine A and mycophenolate mofetil as additional GVHD prophylaxis. All patients in the ATG group homogeneously received a reduced intensity conditioning regimen with fludarabine, 2-day bulsulfan. GVHD prophylaxis was ATG (5mg/kg thymoglobulin) and cyclosporine A. G-CSF from day+5 to neutrophil recovery was given in the PT-Cy group while no patient in the ATG received G-CSF. The day-100 cumulative incidence of grade 2-4 acute GVHD was significantly lower in the PT-Cy group (23% vs. 45%, p=0.014, Figure A). We observed a trend for a lower 2-year cumulative incidence of all grades and moderate to severe chronic GVHD in the PT-Cy group (all grades: 13% vs 33%, p=0.063, Figure B; moderate to severe: 10% vs. 27%, p=0.079). No significant difference was observed in the incidence of relapse (20% in the PT-Cy group vs 11% in the ATG group, p=0.382), non-relapse mortality (3% vs 11%, p=0.203), progression free survival (77% vs 78%, p=0.912) and overall survival (86% vs 83%, p=0.58). All patients engrafted in both groups. Median time from allo-SCT to neutrophil (>0.5G/L) and platelet (>20G/L) recovery was significantly delayed in the PT-Cy group (neutrophil: 19 vs 17 days, p=0.049; platelets: day 26 vs 10, p<0.001). Finally, we followed the GVHD and the immunosuppressive treatment (IST) prevalences in disease free patients as a surrogate marker of quality of life. At 6 months post allo-HSCT, 5% and 36% of the disease-free patients in the PT-Cy group were living with GVHD and IST, respectively. Corresponding values for the ATG group were 26% and 64% for the prevalence of GVHD and IST, respectively. Image:Summary/Conclusion: These data suggest that the PT-Cy platform is an effective GVHD prophylaxis for the 10/10 UD allo-HSCT patients. It significantly decreases the risk of acute GVHD compared with standard prophylaxis with ATG, without increasing the risk of relapse. This study adds to the experience in the HRD and MMUD allo-HSCT, where PT-Cy seems to counterbalance the impact of HLA disparity, leading to promising survivals such as after HLA matched allo-HSCT.